PUBLICATION
Heparan Sulfate as a Therapeutic Target in Tauopathies: Insights From Zebrafish
- Authors
- Alavi Naini, S.M., Soussi-Yanicostas, N.
- ID
- ZDB-PUB-190109-10
- Date
- 2018
- Source
- Frontiers in cell and developmental biology 6: 163 (Review)
- Registered Authors
- Soussi-Yanicostas, Nadia
- Keywords
- Alzheimer’s disease, drug discovery, glycosaminoglycans, heparan sulfate, tau, tauopathy, zebrafish
- MeSH Terms
- none
- PubMed
- 30619849 Full text @ Front Cell Dev Biol
Citation
Alavi Naini, S.M., Soussi-Yanicostas, N. (2018) Heparan Sulfate as a Therapeutic Target in Tauopathies: Insights From Zebrafish. Frontiers in cell and developmental biology. 6:163.
Abstract
Microtubule-associated protein tau (MAPT) hyperphosphorylation and aggregation, are two hallmarks of a family of neurodegenerative disorders collectively referred to as tauopathies. In many tauopathies, including Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and Pick's disease, tau aggregates are found associated with highly sulfated polysaccharides known as heparan sulfates (HSs). In AD, amyloid beta (Aβ) peptide aggregates associated with HS are also characteristic of disease. Heparin, an HS analog, promotes misfolding, hyperphosphorylation and aggregation of tau protein in vitro. HS also provides cell surface receptors for attachment and uptake of tau seeds, enabling their propagation. These findings point to HS-tau interactions as potential therapeutic targets in tauopathies. The zebrafish genome contains genes paralogous to MAPT, genes orthologous to HS biosynthetic and chain modifier enzymes, and other genes implicated in AD. The nervous system in the zebrafish bears anatomical and chemical similarities to that in humans. These homologies, together with numerous technical advantages, make zebrafish a valuable model for investigating basic mechanisms in tauopathies and identifying therapeutic targets. Here, we comprehensively review current knowledge on the role of HSs in tau pathology and HS-targeting therapeutic approaches. We also discuss novel insights from zebrafish suggesting a role for HS 3-O-sulfated motifs in tau pathology and establishing HS antagonists as potential preventive agents or therapies for tauopathies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping